In the medical field, wound repair and post-op body growth and regeneration are correlated pathological and physiological processes, which involve a series of biochemical, physiological, and morphological changes in the body. Thus, defects often appear on skin and organ surfaces when the body is wounded. In the case where cells are unrecoverable, conditions such as infection, festering, or necrosis of transferred flaps and transplanted skin grafts may occur on the body. Generally, in order to lower the possibility of such phenomena, anti-infection treatment methods are often employed in clinical scenarios, for example, by injecting antibiotics or by externally applying traditional Chinese medicine and western medicine, but the survival rate of tissue cells on the wound surface of the body is very low which results in adverse conditions like muscle defects, scar formation, and an extended period of wound healing and even necessitates re-operation.
To solve the technical problem of how to avoid adverse conditions in wounds and lower the re-operation rate, extensive studies and clinical applications in relation to use of the repairing effect of growth factors on body wounds and post-op body tissues have been conducted since 1980s. The concept of body tissue repair has thus developed from the simple healing of body surfaces to the repair process of cells and tissues, which improves or restores the effect of tissue cell survival by using growth factors to manually intervene in the natural healing of wound surfaces.
Collagen, a structural protein constituting the extracellular matrix, is present as white, transparent, non-branched fibrils made up of several types of glycoprotein molecules and has a quaternary structure. The unit of collagen is tropocollogen, the molecule of which is a slim, triple-stranded helical chain having a diameter of 1.5 nm and a length of 300 nm as measured by electron microscopy and having a relative molecular mass of 2.85×105. It has a stable triple-helix spatial structure due to its special amino-acid composition. Collagen is hemostatic, low antigenic, degradable and biocompatible, and is used to make biomedical materials and also to clinically stop bleeding and promote cell growth.
Fibroblast growth factors (FGF) are mitogenic, chemotactic, and regulatory proteins in all cells associated with wound healing, and promote the repair and regeneration of mesoderm- and ectoderm-derived cells (e.g., epithelial cells, hypodermal cells, fibroblasts, and vascular endothelial cells).
US 2006/0236891, US 1978/4,066,083, US 20080268052 and US 2010/7,754,258 disclose methods for preparing collagen membranes by using collagens extracted from Achilles tendons or skin of animals, while none of them mentions measures for virus inactivation. However, in clinical applications, there are always possibilities of cross-infections by pathogenic microorganisms infective to both human and animals, for example, Encephalitis B virus (EBV), Hepatitis E virus (HEV), Pseudorabies virus (PRV), Vesicular stomatitis virus (VSV), and Streptococcus, all of which once caused widespread human-animal cross-infective diseases and disastrous results. Therefore, products manufactured by these preparation methods have certain safety risks in clinical applications.
CN 1228339 and CN1511592 disclose composite collagen sponges incorporated with biological factors, but they employed radiation to carry out disinfection during preparation of these sponges. With respect to bioactive materials, radiation will increase the temperature of the products, resulting in denaturation of the bioactive materials, which not only lowers the activity of the bioactive materials but also leads to generation of new immuno-active materials and therefore causes unnecessary troubles in clinical applications.
Moreover, the activity of the product decreases during long-term storage, which may affect its clinical efficacy and effective life. However, in the abovementioned patent documents, no protecting measures were taken and no investigations were performed regarding the stability of the incorporated bioactive materials, and virus inactivation effectiveness was not verified either.